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Background: Severe neonatal inflammatory conditions in very preterm infants (VPT:

Introduction: This study investigated whether internalizing and externalizing behavioral problems in children were associated with fractional anisotropy of white matter tracts connecting other brain regions to the frontal lobes. We contrasted patterns of association between children born at term (FT) and very preterm (PT: gestational age at birth =< 32 weeks). Methods: Parents completed the Child Behavior Checklist/6–18 questionnaire to quantify behavioral problems when their children were age 8 years (N = 36 FT and 37 PT). Diffusion magnetic resonance scans were collected at the same age and analyzed using probabilistic tractography. Multiple linear regressions investigated the strength of association between age-adjusted T-scores of internalizing and externalizing problems and mean fractional anisotropy (mean-FA) of right and left uncinate, arcuate, anterior thalamic radiations, and dorsal cingulate bundle, controlling for birth group and sex. Results: Models predicting internalizing T-scores found significant group-by-tract interactions for left and right arcuate and right uncinate. Internalizing scores were negatively associated with mean-FA of left and right arcuate only in FT children (pleft AF = 0.01, pright AF = 0.01). Models predicting externalizing T-scores found significant group-by-tract interactions for the left arcuate and right uncinate. Externalizing scores were negatively associated with mean-FA of right uncinate in FT (pright UF = 0.01) and positively associated in PT children (pright UF preterm = 0.01). Other models were not significant. Conclusions: In children with a full range of scores on behavioral problems from normal to significantly elevated, internalizing and externalizing behavioral problems were negatively associated with mean-FA of white matter tracts connecting to frontal lobes in FT children; externalizing behavioral problems were positively associated with mean-FA of the right uncinate in PT children. The different associations by birth group suggest that the neurobiology of behavioral problems differs in the two birth groups.

Abstract Background Infants born very preterm (

Many diffusion magnetic resonance imaging (dMRI) studies document associations between reading skills and fractional anisotropy (FA) within brain white matter, suggesting that efficient transfer of information across the brain contributes to individual differences in reading. Use of complementary imaging methods can determine if these associations relate to myelin content of white matter tracts. Compared to children born at term (FT), children born preterm (PT) are at risk for reading deficits. We used two MRI methods to calculate associations of reading and white matter properties in FT and PT children. Participants (N=79: 36 FT and 43 PT) were administered the Gray's Oral Reading Test at age 8. We segmented three dorsal (left arcuate and bilateral superior longitudinal fasciculus) and four ventral (bilateral inferior longitudinal fasciculus and bilateral uncinate) tracts and quantified (1) FA from dMRI and (2) R1 from quantitative T1 relaxometry. We examined correlations between reading scores and these metrics along the trajectories of the tracts. Reading positively correlated with FA in segments of left arcuate and bilateral superior longitudinal fasciculi in FT children; no FA associations were found in PT children. Reading positively correlated with R1 in segments of the left superior longitudinal, right uncinate, and left inferior longitudinal fasciculi in PT children; no R1 associations were found in FT children. Birth group significantly moderated the associations of reading and white matter metrics. Myelin content of white matter may contribute to individual differences in PT but not FT children.

Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome.In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract.Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p = 0.01, Cohen’s d = 0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1–4 month follow up (0.325 vs 0.512, p = 0.042, d = 1.36) and at the 1-year follow up (0.342, vs 0.484, p = 0.038, d = 1.12).High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.

Aim: To determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications. Method: 30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development–III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes. Results: FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post-menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract. Conclusion: Language at age 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

Children born preterm (PT) are at risk for white matter injuries based on complications of prematurity. They learn to read but on average perform below peers born full term (FT). Studies have yet to establish whether properties of white matter pathways at the onset of learning to read are associated with individual variation later in reading development in PT children. Here, we asked whether fractional anisotropy (FA) at age 6 years is associated with reading outcome at age 8 years in PT children in the same pathways as previously demonstrated in a sample of FT children. PT (n = 34, mean gestational age = 29.5 weeks) and FT children (n = 37) completed diffusion MRI and standardized measures of non-verbal IQ, language, and phonological awareness at age 6 years. Reading skills were assessed at age 8 years. Mean tract-FA was extracted from pathways that predicted reading outcome in children born FT: left arcuate fasciculus (Arc), bilateral superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP). We explored associations in additional pathways in the PT children: bilateral inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. Linear regression models examined whether the prediction of reading outcome at age 8 years based on mean tract-FA at age 6 years was moderated by birth group. Children born PT and FT did not differ significantly in tract-FA at age 6 years or in reading at age 8 years. Sex, socioeconomic status, and non-verbal IQ at age 6 years were associated with reading outcome and were included as covariates in all models. Birth group status significantly moderated associations between reading outcome and mean tract-FA only in the left Arc, right SLF, and left ICP, before and after consideration of pre-literacy skills. Microstructural properties of these cerebral and cerebellar pathways predicted later reading outcome in FT but not in PT children. Children born PT may rely on alternative pathways to achieve fluent reading. These findings have implications for plasticity of neural organization after early white matter injury.

Aim: We previously observed a complex pattern of differences in white matter (WM) microstructure between preterm-born (PT) and full-term-born (FT) children and adolescents age 9–17years. The aim of this study was to determine if the same differences exist as early as age 6years. Method: We obtained diffusion MRI (dMRI) scans in children born PT at age 6years (n=20; 11 males) and FT (n=38; 14 males), using two scanning protocols: 30 diffusion directions (b=1000s/mm2) and 96 diffusion directions (b=2500s/mm2). We used deterministic tractography and analyzed fractional anisotropy (FA) along bilateral cerebral WM pathways that demonstrated differences in the older sample. Results: Compared to the FT group, the PT group showed (1) significantly decreased FA in the uncinate fasciculi and forceps major and (2) significantly increased FA in the right anterior thalamic radiation, inferior fronto-occipital fasciculi, and inferior longitudinal fasciculi. This pattern of group differences resembles findings in the previous study of older PT and FT participants. Group differences were similar across dMRI acquisition protocols. Interpretation: The underlying neurobiology driving the pattern of PT-FT differences in FA is present as early as age 6years. Generalization across dMRI acquisition protocols demonstrates the robustness of group differences in FA. Future studies will use quantitative neuroimaging techniques to understand the tissue properties that give rise to this consistent pattern of WM differences after PT birth. Keywords: Diffusion tensor imaging, White matter, Prematurity, Development, Tractography

Objective: We combined diffusion MRI (dMRI) with quantitative T1 (qT1) relaxometry in a sample of school-aged children born preterm and full term to determine whether reduced fractional anisotropy (FA) within the corpus callosum of the preterm group could be explained by a reduction in myelin content, as indexed by R1 (1/T1) from qT1 scans. Methods: 8-year-old children born preterm (n = 29; GA 22–32 weeks) and full term (n = 24) underwent dMRI and qT1 scans. Four subdivisions of the corpus callosum were segmented in individual native space according to cortical projection zones (occipital, temporal, motor and anterior-frontal). Fractional anisotropy (FA) and R1 were quantified along the tract trajectory of each subdivision and compared across two birth groups. Results: Compared to controls, preterm children demonstrated significantly decreased FA in 3 of 4 analyzed corpus callosum subdivisions (temporal, motor, and anterior frontal segments) and decreased R1 in only 2 of 4 corpus callosum subdivisions (temporal and motor segments). FA and RD were significantly associated with R1 within temporal but not anterior frontal subdivisions of the corpus callosum in the term group; RD correlated with R1 in the anterior subdivision in the preterm group only. Conclusions: Myelin content, as indexed by R1, drives some but not all of the differences in white matter between preterm and term born children. Other factors, such as axonal diameter and directional coherence, likely contributed to FA differences in the anterior frontal segment of the corpus callosum that were not well explained by R1. Keywords: Preterm, Corpus callosum, Fractional anisotropy, Development, myelin

Background: Cognitive outcomes in preterm (PT) children have been associated with microstructural properties of white matter. PT children who experienced neonatal inflammatory conditions have poorer cognitive outcomes than those who did not. The goal of this study was to contrast white matter microstructure and cognitive outcomes after preterm birth in relation to the presence or absence of severe inflammatory conditions in the neonatal period. Methods: PT children (n = 35), born at gestational age 22–32 weeks, were classified as either PT+ (n = 12) based on a neonatal history of inflammatory conditions, including bronchopulmonary dysplasia, necrotizing enterocolitis or culture positive sepsis, or PT- (n = 23) based on the absence of the three inflammatory conditions. Full term (FT) children (n = 43) served as controls. Participants underwent diffusion MRI and cognitive testing (intelligence, reading, and executive function) at age 6 years. The corpus callosum was segmented into 7 regions using deterministic tractography and based on the cortical projection zones of the callosal fibers. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for each segment. General linear models with planned contrasts assessed group differences in FA, MD and cognitive outcomes. Pearson correlations assessed associations of white matter metrics and cognitive outcome measures. Results: FA was significantly lower and MD was significantly higher in PT+ compared to PT- or FT groups in multiple callosal segments, even after adjusting for gestational age. Executive function scores, but not intelligence or reading scores, were less favorable in PT+ than in PT- groups. Among the entire sample, occipital FA was significantly correlated with IQ (r = 0.25, p

Diffusion properties of white matter tracts have been associated with individual differences in reading. Individuals born preterm are at risk of injury to white matter. In this study we compared the associations between diffusion properties of white matter and reading skills in children and adolescents born full term and preterm. 45 participants, aged 9–17 years, included 26 preterms (born

Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.

Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood.

Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.